Understanding the function and regulation of molecules involved in Vascular endothelial growth factor (Vegf) signaling and it's role in blood vessel development have become of increasing significance since the mechanisms that drive this process are the same as those used by vascular pathologies. A better understanding of this developmental process will be key in the development of therapies and diagnoses of many vascular disorders such as heart disease, cancer, and diabetes. The use of a pliable vertebrate genetic system such as the Zebrafish makes the study of blood vessel development both feasible and efficient. In this proposal we single out phospholipase C gamma 1 (plcg1) as the sole integrator of signals derived from Vegf receptors (Vegfr). Through a series of structure function analysis using mutated forms of plcg1 SH2 domains and mutants in plcg1 activation sites, we will determine the necessity of each of these components for blood vessel development, as well as identify key interactions between plcg1 and Vegfrs that are needed to promote this process.
| Villefranc, Jacques A; Nicoli, Stefania; Bentley, Katie et al. (2013) A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development 140:1497-506 |
| Covassin, L D; Siekmann, A F; Kacergis, M C et al. (2009) A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Dev Biol 329:212-26 |
| Villefranc, Jacques A; Amigo, Julio; Lawson, Nathan D (2007) Gateway compatible vectors for analysis of gene function in the zebrafish. Dev Dyn 236:3077-87 |
